#359 ‒ How metabolic and immune system dysfunction drive the aging process, the role of NAD, promising interventions, aging clocks, and more | Eric Verdin, M.D.
Release Date: 08/04/2025
#385 - AMA #82: Applying the tools of longevity in the real world: disease prevention, DEXA scans, artificial sweeteners, injury recovery, stability training, habit formation, protein intake and mTOR activation, and more
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter answers listener questions across a wide range of topics, focusing on practical decision-making and real-world application. He explores how health priorities and strategies should evolve across different decades of life, which chronic diseases are most challenging to manage and how to think about risk hierarchies, and which emerging interventions—beyond exercise—show the most promise for dementia prevention. Peter also breaks down the utility of wearables and explains how to use and interpret DEXA scans effectively. He discusses the...
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#384 - Special episode — Obicetrapib: The CETP inhibitor with cardiovascular benefits and potential Alzheimer's prevention
The Peter Attia Drive
In this special episode, Peter takes a deep dive into obicetrapib, an investigational drug that has captured his attention and renewed interest in an entire class of therapies known as CETP inhibitors. He explains what obicetrapib is and how it works, revisits the history of CETP inhibitors and why earlier versions of these drugs failed—sometimes dramatically—and breaks down the key clinical trials designed to evaluate their impact on cardiovascular risk. Peter examines how obicetrapib influences major lipid biomarkers, including LDL cholesterol and lipoprotein(a) [Lp(a)], and discusses...
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#380 ‒ The seed oil debate: are they uniquely harmful relative to other dietary fats? | Layne Norton, Ph.D.
The Peter Attia Drive
Layne Norton is a nutrition scientist and accomplished power athlete,who returns to The Drive for a conversation that departs from the show’s usual format. In this episode, Layne presents the evidence-based case that seed oils are not uniquely harmful under isocaloric conditions, while Peter steelmans the strongest versions of the opposing argument that seed oils are inherently harmful. They examine how scientific bias and evidence are evaluated, revisit the historical randomized controlled trials that shaped the seed oil controversy, and explore the mechanistic biology underlying LDL...
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#379 - AMA #79: A guide to cardiorespiratory training at any fitness level to improve healthspan, lifespan, and long-term independence
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter brings together his most up-to-date thinking on cardiorespiratory fitness into a single, practical guide designed to help listeners structure training for maximal impact on healthspan, lifespan, and long-term independence. He explains why cardiorespiratory fitness is one of the strongest modifiable predictors of longevity, clarifies what zone 2 training actually represents and how it differs from higher-intensity work, and addresses persistent confusion around exercise volume, intensity, and time constraints. The discussion covers how to...
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#378 ‒ Women’s health and performance: how training, nutrition, and hormones interact across life stages | Abbie Smith-Ryan, Ph.D.
The Peter Attia Drive
Abbie Smith-Ryan is a leading researcher in exercise physiology whose work focuses on how training and nutrition influence body composition, metabolism, cardiovascular health, and women’s health across the lifespan, with particular attention on perimenopause and post-menopause. In this episode, Abbie explains how early exercise and play help build the foundation for bone health, muscle development, and cardiorespiratory fitness in girls, as well as how puberty and menstruation shape athletic performance, motivation, and recovery. She also explores how women can tailor training and...
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Building & Changing Habits | James Clear (#183 rebroadcast)
The Peter Attia Drive
James Clear is the author of the New York Times bestseller Atomic Habits. His extensive research into human behavior has helped him identify key components of habit formation and develop the “Four Laws of Behavioral Change.” In this episode, James provides insights into how both good and bad habits are formed, including the influence of genetics, environment, social circles, and more. He points to changes one can make to cultivate more perseverance and discipline and describes the profound impact habits can have when tying them into one’s self-identity. Finally, James breaks down his...
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#377 ‒ Special episode: Understanding true happiness and the tools to cultivate a meaningful life—insights from past interviews with Arthur Brooks
The Peter Attia Drive
In this special episode of The Drive, Peter presents a curated “best of” conversation with bestselling author and previous guest Arthur Brooks, organized around four core themes: happiness itself, the forces that undermine it, the tools and practices that help cultivate it, and the courage required to live and love well. The episode brings together the most meaningful moments from two past interviews into a single, focused discussion that distills Brooks’ most insightful ideas and offers practical takeaways for building a life that's both successful and deeply happy. We discuss: ...
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#376 - AMA #78: Longevity interventions, exercise, diagnostic screening, and managing high apoB, hypertension, metabolic health, and more
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter tackles a wide-ranging set of listener questions spanning lifespan interventions, exercise, cardiovascular risk reduction, time-restricted eating, blood pressure management, hormone therapy, diagnostics, and more. Peter reveals the single most important lever for extending healthspan and lifespan, and explains how he motivates midlife patients using the Centenarian Decathlon framework. He discusses the importance of addressing high apoB and cholesterol even in metabolically healthy individuals with calcium scores of zero, how to manage high...
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#375 - Ketogenic diet, ketosis & hyperbaric oxygen: metabolic therapies for weight loss, cognition, Alzheimer’s & more | Dom D’Agostino, Ph.D.
The Peter Attia Drive
Dom D'Agostino is a neuroscientist and professor at the forefront of metabolic therapies, including ketogenic diets, exogenous ketones, and hyperbaric oxygen. In this episode, Dom breaks down nutritional versus supplemental ketosis, defines meaningful ketone thresholds, and outlines practical ways to achieve ketosis. He explains how a ketogenic diet can support metabolic health and weight loss, and advises on how to maintain adequate protein and avoid common mistakes. Dom surveys the growing landscape of exogenous ketones—from salts and esters to 1,3-butanediol—and effective pairings...
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#374 - The evolutionary biology of testosterone: how it shapes male development and sex-based behavioral differences, | Carole Hooven, Ph.D.
The Peter Attia Drive
Carole Hooven is a human evolutionary biologist whose research centers on testosterone, sex differences, and behavior. In this episode, she explores how prenatal testosterone orchestrates male development in the body and brain, how early hormonal surges shape lifelong behavioral tendencies, and what rare natural experiments—such as 5-alpha-reductase deficiency—reveal about the biology of sex differentiation. She discusses distinct male and female aggression styles through an evolutionary lens, how modern environments interact with ancient competitive drives, and the implications of...
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Eric Verdin is a physician-scientist and the CEO of the Buck Institute for Research on Aging whose career has centered on understanding how epigenetics, metabolism, and the immune system influence the aging process. In this episode, Eric traces his scientific journey from studying viruses and histone deacetylases (HDACs) to leading aging research at the Buck Institute, offering insights into how aging impairs immune and nervous system function—including thymic shrinkage, chronic inflammation, and reduced vaccine response—and how these changes impact lifespan. He explores the metabolic underpinnings of aging, such as oxidative stress and insulin and IGF-1 signaling, and he discusses practical tools like zone 2 cardio, ketogenic diets, and GLP-1 drugs. The conversation also covers declining NAD levels with age, the roles of NAD-consuming enzymes such as sirtuins and CD38, and what current NAD-boosting strategies (like NMN, NR, and IV NAD) can and can’t accomplish. Eric weighs in on promising longevity interventions including rapamycin, growth hormone for thymic regeneration, and anti-inflammatory therapies, while also examining the promise and limitations of current biological age tests and the potential of combining epigenetic, proteomic, and organ-specific metrics with wearables to guide personalized longevity care.
We discuss:
- Eric’s scientific journey from virology to the field of geroscience [2:45];
- How dysfunction in the immune system and central nervous system can drive aging throughout the body [5:00];
- The role of metabolism and oxidative stress in aging, and why antioxidant strategies have failed to deliver clear benefits [8:45];
- Other aspects of metabolism linked to aging: mitochondrial efficiency, fuel utilization, and glucose-modulating drugs [16:30];
- How inefficient glucose metabolism drives insulin, IGF-1 signaling, and accelerates aging [21:45];
- The metabolic effects of GLP-1 agonists, and the need to move beyond crude metrics like BMI in favor of more precise assessments of metabolic health [27:00];
- The case for immune health as a “fifth horseman” [36:00];
- How the innate and adaptive immune systems work together to build immune memory [39:45];
- Why vaccines lose effectiveness with age: shrinking of the thymus gland and diminished T-cell diversity [44:15];
- Exploring growth hormone, thymic regeneration, and the role of exercise in slowing immune aging [48:45];
- The challenges of identifying reliable biomarkers for immune function, and the potential of rapamycin analogs to enhance vaccine response in older adults [57:45];
- How rapamycin’s effects on the immune system vary dramatically by dosage and frequency [1:03:30];
- The limitations of mouse models in aging research and the need for cautious interpretation of rapamycin’s benefits in humans [1:08:15];
- NAD, sirtuins, and aging: scientific promise amid commercial hype [1:15:45];
- How CD38 drives age-related NAD decline, influences immune function, and may impact longevity [1:23:45];
- How NMN and NR supplementation interact with CD38 and NAD metabolism, and potential risks like homocysteine elevation and one-carbon cycle depletion [1:31:00];
- Intravenous NAD: limited evidence and serious risks [1:37:00];
- Interleukin-11 (IL-11) as a new target in immune aging, the dual role of chronic inflammation in aging, and the need for better biomarkers to guide interventions [1:43:00];
- Biological aging clocks: types of clocks, promise, major limitations, and future outlook [1:48:30];
- The potential of proteomics-based aging clocks for detecting organ-specific decline and frailty [2:00:45]; and
- More.
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